DPP-4 inhibition improves a sexual condition?

Erectile dysfunction (ED) is a condition of persistent inability to achieve or maintain an erection sufficient for satisfactory sexual intercourse. The etiology of ED is predominantly vascular, explained by nitric oxide metabolism disturbances being in the background. Nitric oxide enhancing drugs like phosphodiesterase 5 inhibitors, which delay the breakdown of nitric oxide, are widely used, but still without complete success. Restauration of endogenous nitric oxide production focused on improving endothelial dysfunction could be a more effective way of treatment, addressing also other vessels in the body and preventing more serious cardiovascular disease. Endothelial progenitor cells are bone marrow-derived cells found also in human circulation, and may under circumstances be embedded into the vascular intima leading to improvements in nitric oxide production and thus in endothelial function in many organs, including the penis. In this article we hypothesize the potential role of DPP-4 inhibitors, a novel class of antidiabetic drugs in increasing the number of circulating endothelial progenitor cells. Speculated mechanisms include several substrates for DPP-4 inhibitors: GLP-1, SDF-1α, substance P, and PACAP. As DPP-4 inhibitors show favorable safety profiles and do not cause hypoglycemia, they seem to be an attractive treatment option, at least in diabetic patients, and could become a part of vascular regenerative pharmacotherapy, ameliorating also symptoms related to erectile dysfunction. Since erectile dysfunction may precede other cardiovascular vascular events, because the penile arteries are smaller in size and therefore more susceptible to decreased nitric oxide production, treating this condition with an agent affecting positively also other blood vessels could help in preventing other cardiovascular events, including myocardial infarction and stroke. However, caution is required, because DPP-4 inhibitors are a heterogenous class of drugs, with variations regarding strength and duration of action, as well as selectivity and cardiovascular safety profile, which may affect properties other than those important in glucocontrol.